Substance Abuse

Drug Site of Action/MOA Effect

Lipid Soluble; one of the MOST highly addictive drugs In low doses, Nicotine causes ganglion stimulation At high doses, Nicotine causes ganglion blockade

Treatment of Cessation/ Withdrawal

Nicotine chewing gum is approved by the FDA for the treatment of nicotine dependence Nicotine transdermal patch Bupropion (Zyban) is used to the craving (DA reuptake) Varenicline (chantix) is a nicotinic receptor partial agonist used in tx of smoking cessation

Toxic Effects/ NB:

Cigarette smoke is primarily composed of nicotine and a dozen other gases, mainly CO, which the risk of lung cancer, emphysema, and bronchial disorder Women older than 30, who smoke and also take oral contraceptives are more prone to cardiovascular diseases than other Toxic Psychosis d/t cocaine is characterized by auditory and tactile hallucinations Cocaine related deaths are often of cardiac arrest or seizures Cocaine is available as hydrochloride salts and free base crack (when consumed by different forms it reaches concentration in the plasma at different rates Ex: By IV or inhalation it reaches levels in plasma quickly which is associated with high dependence) Can cause palpitations and cardiac arrhythmias Chronic use leads to schizophrenic-like conditions (i.e. Paranoia) Overdose can result in brain damage, tactile hallucinations, and *rhabdomyolysis

Nicotine

Nicotine mimics the actions of Ach at nicotinic receptors and directly activates DA cells

Cocaine is a strong CNS stimulant that interferes with NE, 5HT and esp. DA reuptake into the presynaptic nerve terminal; This blockade results in enhanced activity of these tissues Powerful neuropsychological reinforcing property Cocaine causes vasoconstriction, dilated pupils, and temperature, heart rate and blood pressure Can be used as a local anesthetic & vasoconstrictor during ENT procedures (MOST anesthetics are vasodilators) Acute effects include: alertness, concentration, libido and jaw clenching Has a high abuse potential b/c it enters the brain very quickly Dextromethamphetamine is used to treat ADHD, narcolepsy, and obesity

Cocaine

The release of DA, NE and 5HT MDMA reverses the effects of the SERT, NET & DAT Transporters essentially releasing these monoamines into the synapse instead of taking it up MDMA indirectly releases oxytocin (responsible for events like hugging, orgasm & childbirth) & facilitates bonding & trust Acts on GABAA Channel to the frequency of channel opening

Amphetamine

MDMA (Ecstacy)

Synthetic psychoactive drug similar to methamphetamine Primary effects: warmth, feeling of openness, euphoria, *empathy, sexual pleasure Acute Effect = Excitation Chronic Effect = Depression

MDMA can interfere with the ability to regulate temperature. This can lead to hyperthermia resulting in kidney and cardiovascular failure Chronic MDMA exposure leads to damage to 5HT neurons leading to s/s of depression

Benzodiazepines Flunitrazepam (Rophepnol)

Powerful hypnotic drug that is a benzodiazepine derivative (used to be used for Insomnia on a short term basis) Produces anterograde amnesia

Antidote = Flumazenil

Not available medically in US b/c often used as a date rape drug; It can incapacitate victims and prevents them from resisting sexual assault when mixed w/alcohol

Phencyclidine (PCP)

Acts by blocking NMDA Receptors

Lysergic acid diethylamide (LSD)

Activates 5HT receptors in the neocortex, limbic system and brainstem

Popular hallucinogen angel dust Alters mood in an unpredictable fashion, individuals can become animated, acts of self-injury like suicide, and attacks on others or destruction of property may be seen *Violence, Decreased pain sensation Also induce psychotic reactions Potent hallucinogen that produces illusions, visual, auditory & olfactory hallucinations *Synesthesia: Sensations may seem to cross over giving the feeling of hearing colors and seeing sounds; these changes can be frightening and can cause panic these can be referred to as a bad trip Flashbacks are a psychological phenomenon in which an individual experiences an episode of some of LSDs subjective effects long after the drug has worn off The most commonly used illicit drug in the USA Dronabinol, synthetic cannabis is used as an anti-emetic and appetite stimulant (could tx Anorexia) Potential therapeutic effects include its ability to Intraocular Tension (Treatment of Glaucoma) Short Term Psychoactive Effects: *Euphoria, anxiety, and memory loss (psychomotor activity, impaired judgment, memory & time sense)

Chronic use can cause memory loss, difficulties with speech and thinking, and they persist even after stopping PCP Overdose of PCP includes dilated pupils,* nystagmus, hypertension

Synesthesias Flashbacks

The main active chemical in marijuana is THC (delta-9tetrahydrocannabinol)

Marijuana

Somatic effects include: Tachycardia, dry mouth, *Redness of eyes (congestion of conjunctival blood vessels), Bronchodilation, Appetite Marijuana is implicated as the cause of amotivational syndrome At high doses can cause depression

Drug Intoxication Amphetamine Cocaine Phencyclidine Opioids LSD

Hallmark feature Paranoia, Picking at skin Arrhythmia, vasoconstriction Violence,Vertical Nystagmus, Decreased Pain Pinpoint Pupil Flashback, Synesthia

**Remember to Read Alcohol Abuse Lecture** Abuse of a drug is construed as any use of a drug for non-medical purposes, usually for altering consciousness and or/body building Psychological dependence Manifested by compulsive drug-seeking behavior for personal satisfaction, often in the face of known health risk. Deprivation of the agent results in craving The release of DA and activation of the pleasure reward pathway is responsible for the psychological dependence The pleasure reward pathway includes the dopaminergic pathway from the ventral tegmental area (VTA) to the nucleus accumbens (NA) and extending to the prefrontal cortex Physical dependence A physiological state of adaptation characterized by the tolerance to the drug effects and emergence of a withdrawal syndrome during abstinence Continuous consumption of drug results in tolerance and the increased dose of the drug; if you take the drug away it tries to act like a pathological disease and it results in withdrawal syndrome (Mydriasis etc..)